The Core continues to be a part of the Metabolic Clinical Research Unit (MCRU), which was established at NIH in 2007 under the first NIH Strategic Plan for Obesity Research. It is design to conduct research to identify potential causes and evaluate treatments of obesity. Currently 1/3 of the adult US population is obese and another 1/3 are overweight. Obesity is a major cause of diabetes, cardiovascular disease, and some cancers, yet our understanding of obesity physiology is rudimentary. Since 2007, the obesity epidemic has continued unabatedthe need for rigorous and properly controlled metabolic research is even more important. At NIH, much of the research is conducted on the MCRU that consists of the 5SW-N (inpatient) unit, 5SW-S (day hospital), and 7SW-S whole room calorimetry suites, which includes a special room with a DXA body composition scanner, and Bod Pod. An exercise testing room and portable activity measurements are also a component of the Core function. Research highlights: 1. In patients with lipodystrophy, leptin cannot be secreted endogenously, which results in profound metabolic dysfunctions. Recombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities. We worked with Drs. Rebecca Brown and Phillip Gorden from the NIDDK Diabetes, Endocrinology, and Obesity Branch, and measured whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant. In a recent paper, we show that metreleptin improves insulin sensitivity and decreases hepatic and circulating triglycerides and that these improvements are independent of its effects on food intake and energy expenditure. 2. We have been collaborated with Dr. Yaron Rotman from the NIDDK Liver Disease Branch to study patients with chronic liver disease including non-alcoholic fatty liver disease. We sought to examine whether disturbances in central and peripheral circadian rhythms were related to the experience of fatigue in patients by measuring sleep and activity using wearable monitors. Subtle aberrations in melatonin and adrenal circadian rhythms, as well as reduced sleep efficiency, were founds to likely contribute to fatigue in these patients. These abnormalities may ultimately be a therapeutic target to improve quality of life for fatigued patients with chronic liver diseases. 3. We have been interested in studying childhood obesity since the establishment of the Core. We continue to contribute to the studies with Dr. Jack Yanovskis research group from NICHD. In a recent paper, we investigated whether interrupting sedentary behavior (sitting) with very short periods of walking would improve glucose metabolism without affecting dietary intake in children with overweight or obesity in a randomized controlled trial. In 35 children 7-11 years of age, we showed that, as compared to prolong sitting (3 hrs), interrupting sitting with brief moderate-intensity walking (3 min every 30 mins) significantly improved glucose metabolism without significantly increasing energy intake in children with overweight or obesity. Clinically, interrupting sedentary behavior may be a promising intervention strategy for reducing metabolic risk in such children. 4. We continue to collaborate with researchers around the world to improve the understanding of how physical activity and sleep in different populations. We published two papers with studies on the health of older adults (Iceland and Australia), one in middle-aged adults (US), and two in youth (Iceland). The objective measurements of free-living physical activity and sleep have helped us to better understand their potential impacts to the overall health in these populations. The Core continues to support 29 clinical protocols and protocols from 14 different IC's of the NIH. Services rendered (FY18 activities): energy expenditure by whole-room respiratory chambers (288), resting energy expenditure by metabolic carts (413), graded-exercise tests (68), experimental food behavior tests (430), and body composition (197 DXA, 81 Bod Pod).